Evidence that the lipid moiety of oxidized low density lipoprotein plays a role in its interaction with macrophage receptors.
The binding of oxidatively damaged red blood cells (OxRBCs) to resident mouse peritoneal macrophages correlates with an increase in phosphatidylserine on the external leaflet of the plasma membrane. Liposomes rich in phosphatidylserine can inhibit this binding and also the binding of certain apoptotic cells. We have shown previously that oxidized low density lipoproteins (OxLDL) also can inhibit the binding of OxRBCs to resident mouse peritoneal macrophages. The present studies show that microemulsions prepared from the lipids extracted from OxLDL are very effective in inhibiting the binding of OxRBCs and also, to a lesser extent, of apoptotic thymocytes to macrophages. OxRBC binding was also inhibited by cholesterol phospholipid liposomes containing oxidized 1-stearoyl-2-linoleoyl-phosphatidylcholine. The binding and uptake of 125I-labeled OxLDL were also strongly inhibited by microemulsions of the lipids extracted from OxLDL and by cholesterol phospholipid liposomes containing oxidized 1-palmitoyl-2-arachidonoyl-phosphatidylcholine. Earlier studies have shown that the delipidated protein moiety of OxLDL can competitively inhibit macrophage binding of intact OxLDL, implicating the protein moiety as an effective receptor-binding domain of OxLDL with respect to some macrophage scavenger receptors. The present studies suggest that the lipid moiety of OxLDL may also play a role.
Terpstra
V
V
Department of Medicine 0682, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0682, USA.
Bird
D A
DA
Steinberg
D
D
D000818:Animals; D001055:Apolipoproteins B / Q000378:metabolism; D004655:Emulsions; D006801:Humans; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008081:Liposomes; D017737:Macrophages, Peritoneal / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D010587:Phagocytosis; D011971:Receptors, Immunologic / Q000378:metabolism*; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D013329:Structure-Activity Relationship
D001055:Apolipoproteins B; D004655:Emulsions; D008077:Lipoproteins, LDL; D008081:Liposomes; D008565:Membrane Proteins; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C032629:acetyl-LDL; C099252:oxidized low density lipoprotein